CCG-1423 is a specific inhibitor of Rho pathway-mediated signalling and activation of serum response factor (SRF) transcription. The Rho family of small GTPases play a vital role in transduction of cell signalling events associated with several human cancers. It inhibits SRF-driven luciferase expression in PC-3 cells following stimulation with constitutively active Gα13 with an IC50 value of 1 μM. The site of inhibition in the pathway is not precisely defined but CCG-1423 appears to act on some aspect of the interaction of SRF with its transcriptional cofactor megakaryoblastic leukemia 1 (MKL1) at a point upstream of DNA binding. CCG-1423 selectively inhibits DNA synthesis, proliferation and invasion of Rho-overexpressing cell lines at nanomolar to low micromolar concentrations.
